PSB0788 ameliorates maternal inflammation-induced periventricular leukomalacia-like injury.

Yilu Li, Dan Wang, Zhuoyang Li, Zhi Ouyang

Bioengineered 2022 Apr

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Studies have shown that periventricular leukomalacia (PVL) is a distinctive form of cerebral white matter injury that pertains to myelination disturbances. Maternal inflammation is a main cause of white matter injury. Intrauterine inflammation cellular will be propagated to the developing brain by the entire maternal-placental-fetal axis, and triggers neural immune injury. As a low-affinity receptor, adenosine A2B receptor (A2BAR) requires high concentrations of adenosine to be significantly activated in pathological conditions. We hypothesized that in the maternal inflammation-induced PVL model, a selective A2BAR antagonist PSB0788 had the potential to prevent the injury. In this work, a total of 18 SD pregnant rats were divided into three groups, and treated with intraperitoneal injection of phosphate buffered saline (PBS), lipopolysaccharide (LPS), or LPS+PSB0788. Placental infection was determined by H&E staining and the inflammatory condition was determined by ELISA. Change of MBP, NG2 and CC-1 in the brain of the rats' offspring were detected by western blot and immunohistochemistry. Furthermore, LPS-induced maternal inflammation reduced the expression of MBP, which related to the decrease in the numbers of OPCs and mature oligodendrocytes in neonate rats. After treatment with PSB0788, the levels of MBP proteins increased in the rats' offspring, improved the remyelination. In conclusion, our study shows that the selective A2BAR antagonist PSB0788 plays an important role in promoting the normal development of OPCs in vivo by the maternal inflammation-induced PVL model. Future studies will focus on the mechanism of PSB0788 in this model.

Citation

Yilu Li, Dan Wang, Zhuoyang Li, Zhi Ouyang. PSB0788 ameliorates maternal inflammation-induced periventricular leukomalacia-like injury. Bioengineered. 2022 Apr;13(4):10224-10234